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BACKGROUND: Some previous studies have shown that weight gain is associated with greater improvement in psychopathology during antipsychotic treatment in patients with chronic schizophrenia. However, the results are mixed due to many confounding factors. The current study aimed to investigate whether weight gain was associated with antipsychotic response in patients with antipsychotic-naive and first-episode (ANFE) DSM-IV--diagnosed schizophrenia. METHODS: 526 ANFE patients and 313 healthy controls were enrolled in this study, which was conducted from January 2012 to December 2018. Treatment outcome was measured by the Positive and Negative Syndrome Scale (PANSS) at baseline and follow-up. Weight was measured at baseline and at the end of 8 weeks. RESULTS: After treatment, PANSS scores were significantly reduced as follows: positive symptoms (-10.40; 95% CI, -9.31 to -10.60), negative symptoms (-5.01; 95% CI, -4.43 to -5.54), general psychopathology (-13.01; 95% CI, -12.01 to -14.01), and PANSS total score (-28.53; 95% CI, -26.73 to -30.33). In addition, the average weight of ANFE patients increased by 2.89 kg (95% CI, 2.55 to 3.22), although it was still lower than the average weight of healthy controls. The proportion of patients with weight gain ≥ 7% after treatment was 38.2%. Weight gain was positively associated with decrease of PANSS positive symptoms, general psychopathology, and total score (all P < .05). Multiple linear regression analysis showed that baseline weight, decrease of PANSS total score, and sex were significantly associated with weight gain after treatment. CONCLUSIONS: Our findings suggest that there is a significant association between weight gain and improvement of clinical symptoms after 8 weeks of antipsychotic treatment in patients with ANFE schizophrenia. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04076371.
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Antipsicóticos/farmacología , Evaluación de Resultado en la Atención de Salud , Esquizofrenia/tratamiento farmacológico , Esquizofrenia/fisiopatología , Aumento de Peso/efectos de los fármacos , Adulto , Antipsicóticos/administración & dosificación , Antipsicóticos/efectos adversos , Femenino , Estudios de Seguimiento , Humanos , Masculino , Estudios Prospectivos , Escalas de Valoración Psiquiátrica , Índice de Severidad de la Enfermedad , Adulto JovenRESUMEN
OBJECTIVE: To investigate the safety and efficacy of tumor-associated antigen-specific cytotoxic T lympho- cytes (TAA-CTL) in the treatment of multiple myeloma (MM) and non-Hodgkin lymphoma (NHL). METHODS: Peripheral blood mononuclear cells (PBMNC)of patients were collected. Dendritic cells (DC) were loaded with multiple tumor-associated antigens (TAA) (NY-ESO-1, MAGE-A3, MAGE-A4, WT1, Survivin, PRAME, LMP1 and LMP2A), then co-cultured with PBMNC to induce cytotoxic T lymphocytes (CTL). The phenotypes of cell products were detected, and the disease statuse was evaluated in 7 patients during or after infusion. The changes of TAA-CTL amount in the PBMNC of patients were measured by using IFN-γ ELISpot assay. RESULTS: TAA-CTL products were generated comprising CD3+ T cells (mean 82.98%) with a mixture of CD4+ (mean 42.09%) and CD8+ (mean 25.32%) T cells. Among them, 70% expressed effectors memory markers (CD45RO+CD62L-CCR7-). Each patient received TAA-CTL infusions for 1-4 times, and none of them showed obvious adverse reactions. The clinical symptoms and laboratory or imaging examination of 5 patients achieved positive effects. After cell therapy, the spot-forming cells (SFC) levels of most patients gradually increased and the peak often appeared about 2-3 weeks after the infusion. CONCLUSION: TAA-CTLs preliminarily show its safety and efficacy in MM and NHL patients, however, a larger population sample is needed to explore its clinical application value.
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Linfoma no Hodgkin , Mieloma Múltiple , Células Dendríticas , Humanos , Leucocitos Mononucleares , Linfoma no Hodgkin/terapia , Mieloma Múltiple/terapia , Linfocitos T CitotóxicosRESUMEN
A series of new fluoro-substituted benzimidazole derivatives were designed, synthesized and pharmacologically evaluated. All the target compounds were characterized by 1HNMR, 13CNMR, mass spectra and elemental analysis. The biological evaluation showed that most of the synthesized compounds displayed nanomolar affinity to the angiotensin II type 1 (AT1) receptor and could decrease blood pressure efficiently in spontaneously hypertensive rats. The maximal response of mean blood pressure (MBP) lowered 74.5 ± 3.5 mmHg (1g) and 69.2 ± 0.9 mmHg (2a) at 10 g/kg after oral administration, and the antihypertensive effect lasted beyond 24 h, which performed better than both losartan and telmisartan. So, compounds 1g and 2a may be considered as potential antihypertension drug candidates.
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Antihipertensivos/uso terapéutico , Bencimidazoles/síntesis química , Bencimidazoles/uso terapéutico , Presión Sanguínea/efectos de los fármacos , Animales , Antihipertensivos/farmacología , Diseño de Fármacos , Estructura Molecular , Relación Estructura-ActividadRESUMEN
BACKGROUND: Langerhans cell histiocytosis (LCH) is a rare disease of unknown aetiology. While it may affect any organ of the body, few cases of solitary lung involvement are published in the literature. Here, we report a rare case of pulmonary LCH (PLCH) in an adult. CASE SUMMARY: A 52-year-old male presented to hospital in July 2018 with complaints of progressively worsening cough with sputum, breathlessness, easy fatigability, and loss of appetite since 2016, and a 32-year history of heavy cigarette smoking (average 30 cigarettes/d). Physical examination showed only weakened breathing sounds and wheezing during lung auscultation. Chest computed tomography (CT) showed irregular micronodules and multiple thin-walled small holes. Respiratory function tests showed a slight decrease. Ultrasonic cardiogram showed mild tricuspid regurgitation and no pulmonary hypertension. Fibreoptic bronchoscopy was performed with transbronchial biopsies from the basal segment of right lower lobe. LCH was confirmed by immunohistochemistry. The final diagnosis was PLCH without extra-pulmonary involvement. We suggested smoking cessation treatment. A 3-mo follow-up chest CT scan showed clear absorption of the nodule and thin-walled small holes. The symptoms of cough and phlegm had improved markedly and appetite had improved. There was no obvious dyspnoea. CONCLUSION: Imaging manifestations of nodules, cavitating nodules, and thick-walled or thin-walled cysts prompted suspicion of PLCH and lung biopsy for diagnosis.
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A series of new angiotensin II receptor 1 antagonists were prepared. They displayed nanomolar affinity to AT1 receptor and could decrease blood pressure efficiently in spontaneously hypertensive rats. Among them, compounds 1b and 2b could reduce the blood pressure with more or equal potency compared to Losartan. So, compounds 1b and 2b could be considered as potential antihypertension drug candidates.
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The aim of this study was to investigate the role of F-18 fluoro-2-deoxyglucose positron emission tomography/computed tomography (F-18 FDG PET/CT) in diagnosis and prognostic evaluation of secondary hemophagocytic syndrome (HPS). A total of 11 secondary HPS patients examined with 18F-FDG-PET/CT were retrospectively analyzed. The diagnostic value of F-18 FDG PET/CT for malignancy detection was assessed. The values of maximum standardized uptake value (SUV(max)) in spleen (SUVS(p)) and in bone marrow (SUVBM) were measured to analyze their relationship with various laboratorial parameters and clinical outcome of secondary HPS patients. The results showed that 4 out of the 11 patients had malignancies, the sensitivity, specificity and diagnostic accuracy of F-18 FDG PET/CT for malignancy detection were 100%, 66.7% and 75% respectively, the SUV(max) of spleen and bone marrow showed no significant correlation with laboratorial parameters, a maximum SUVS(p) of 3.10 and a maximum SUVBM of 3.47 were the optimal cutoffs for predicting patients' outcome, the increased uptake of F-18 FDG in the BM and spleen were significantly associated with shorter survival time according to univariate analysis. It is concluded that 18F-FDG PET/CT may especially play an important role in diagnosis and predicting outcome of secondary HPS for the small sample size.
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Linfohistiocitosis Hemofagocítica/diagnóstico por imagen , Tomografía de Emisión de Positrones , Tomografía Computarizada por Rayos X , Fluorodesoxiglucosa F18 , Humanos , Imagen Multimodal , Pronóstico , Estudios RetrospectivosRESUMEN
This study was aimed to explore the immunophenotyping characteristics of acute myeloid leukemia (AML) and their correlation with the curative efficacy. The bone marrow or blood samples were collected from 516 patients with newly diagnosed AML, and their immunophenotypes were analyzed by flow cytometry. The results showed that (1) In 516 cases, the ratios of myeloid antigen expression were higher, as follows: MPO 95.0%, CD33 93.0%, CD13 88.8%, CD117 69.4%; and the expressions of CD14, CD15, CD64 and CD71 were lower, meanwhile 145 cases were accompanied with lymphocyte antigen expression, the ratios were as follows: CD7 21.5%, CD19 6.0%, CD2 0.78%, CD10 0.58% and CD20 0.58%; the positive expression rate of CD71 in M6 was 100%, and that of CD64 in M5 was the highest (30.2%); the overall positive rate of CD34 was 57.8%. (2) After first chemotherapy, the complete remission (CR) rate was 64.7%, CR rate of CD34(+) patients was lower than that of CD34(-) in M3 group (P = 0.019). The CR rate of CD34(+) patients was significantly lower than that of CD34(-) in non-M3 group (P = 0.002). The CR rate of CD19(+) patients was higher than CD19(-) (P = 0.028); the CR rate of CD7(+) patients was significantly lower than that of CD7(-) (P = 0.002); the CR rate of CD71(+) patients was lower than that of CD71(-) (P = 0.013); the CR rate of MPO(+) patients was higher than that of MPO(-) (P = 0.015). Between the CR rate of CD11b, CD13, CD33-positive and-negative group, the difference was not statistically significant (P > 0.05). It is concluded that the phenotype is a prerequisite for the diagnosis of AML, and can help to guide the clinical typing, selection of treatment protocols and evaluation of prognosis.
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Inmunofenotipificación , Leucemia Mieloide Aguda/genética , Adolescente , Adulto , Anciano , Antígenos CD/genética , Femenino , Citometría de Flujo , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/terapia , Masculino , Persona de Mediana Edad , Pronóstico , Resultado del Tratamiento , Adulto JovenRESUMEN
OBJECTIVE: To retrospectively analyze the curative efficacy of umbilical cord blood transplantation (UCBT) with improved myeloablative conditioning regimen (total body irradiation (TBI)/cytosine arabinoside (Ara-c)/cyclophosphamide (CY) without antithymocyte globulin (ATG)) in adult patients with hematological malignancies. METHODS: Forty consecutive adult patients with hematological malignancies received improved myeloablative unrelated CBT at a single center from September 2006 to May 2011. Their average age was (23 ± 6) years and the average weight (58 ± 9) kg. Thirty-five (87.5%) patients were high-risk and 15 (37.5%) at the advanced disease status at pre-transplantation. They received 1 (n = 23) or 2 (n = 17) cord blood units. Seventy-five percent of them were transplanted with 1/2-human leukocyte antigen mismatched unit. The conditioning regimen consisted of 12 Gy TBI, granulocyte colony-stimulating factor (G-CSF) plus Ara-c and CY without ATG. All patients received a combination of cyclosporine (CsA) and mycophenolate mofetil (MMF) for the prophylaxis of graft-versus-host disease (GVHD). RESULTS: For the entire group of patients, the average cell doses infused were (4.1 ± 1.1)×107 total nucleated cells/kg and (2.4 ± 1.0)×105 CD34(+) cells/kg. All patients acquired engraftment with an implantation rate of 100%. The average time of absolute neutrophil count (ANC) ≥ 0.5×109/L was (20 ± 5) days and the average time of platelet ≥ 20×109/L was(38 ± 12) days. Acute GVHD occurred in 23 patients (57.5%) and 4 (10.0%) were of grade III-IV. Chronic GVHD occurred in 22.9% (8/35) evaluable patients. Relapse occurred in 12.5% (5/40) patients. During a median follow-up period of 19.8 (range 4.6 - 55.0) months, the transplantation-related mortality was 15.0% (6/40) within 100 days and 35.0% (14/40) within 1 year. The main causes of mortality were pneumonia and severe acute GVHD. Two-year overall survival (OS) or disease-free survival was 58.8% and 58.8%, respectively. Two-year OS for patients with advanced or complete remission disease was 48.6% and 63.8%, respectively. CONCLUSIONS: The TBI/Ara-c/CY myeloablative conditioning regimen is well-tolerated and capable of establishing sustained donor cell engraftment and decreasing the risks of transplant-related death in adults with hematologic malignancies. For the high-risk and advanced patients, it may reduce the occurrences of relapse and chronic GVHD.
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Trasplante de Células Madre de Sangre del Cordón Umbilical/métodos , Neoplasias Hematológicas/cirugía , Acondicionamiento Pretrasplante/métodos , Adolescente , Adulto , Femenino , Enfermedad Injerto contra Huésped/prevención & control , Humanos , Leucemia/cirugía , Masculino , Irradiación Corporal Total , Adulto JovenRESUMEN
The purpose of study was to investigate the cytogenetic abnormality of acute leukemias (AL), to analyze the relationship in the chromosomal abnormality and the AL FAB types, and to explore the impact of the chromosomal abnormalities on the prognostic factors of AL. The chromosome karyotypes of 397 patients with AL were analyzed by means of bone marrow short-term culture and G banding technique. The results showed that in 319 out of 397 patients, the chromosome karyotypes could be analyzed, and the chromosomal abnormality occurred in 175 patients (54.9%). In the patients with acute lymphocytic leukemia (ALL), acute myelogenous leukemia (AML) and acute mixed-lineage leukemia (AMLL), the chromosomal abnormality occurred respectively in 33 of 120 patients (27.5%), 129 of 252 patients (51.2%) and 13 of 25 patients (52.0%). Hyper-diploids, hypo-diploids and diploids occurred in 41 of 175 patients (23.4%), 22 of 175 patients (12.5%), and 112 of 175 patients (64.0%) respectively. In patients with AML the FAB type-associated chromosomal abnormality occurred in 69 of 129 patients (53.5%). It is concluded that chromosomal abnormalities exist in about 55% AL patients. Some special chromosomal abnormalities are cytogenetic characteristics of AL, and obviously correlated with AL FAB types, the combination of chromosomal detection with cytogenetics is useful for the diagnosis of AL, and the evaluation of therapeutic effects and prognosis.
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Aberraciones Cromosómicas , Cariotipificación , Leucemia/genética , Enfermedad Aguda , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Femenino , Humanos , Cariotipo , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
This study was aimed to investigate the expression of CCAAT/enhancer binding protein alpha gene (c/ebpα) in patients with myelodysplastic syndromes (MDS) and to explore the significance of c/ebpα in pathogenesis and progression of MDS. Real time quantitative reverse transcriptase polymerase chain reaction (RQ-PCR) method was used to detect the expression level of c/ebpα mRNA in bone marrow mononuclear cells (BMMNC) of 33 patients with MDS and 14 normal controls. The results showed that the expression level of c/ebpα mRNA in low-risk and high-risk MDS was significantly lower than that of normal controls (p < 0.01, p < 0.001, respectively), moreover, high-risk MDS showed lower c/ebpα mRNA expression compared with low-risk MDS (p < 0.05). c/ebpα mRNA expression level in MDS was not correlated with sex, age and peripheral blood cell amount, while the ratio of blast cells in bone marrow was in the c/ebpα mRNA low expression group significantly higher than that in the high expression group (p < 0.01). It is concluded that down-regulation of c/ebpα mRNA expression level has closely associated with the pathogenesis of MDS, the c/ebpα may be an important molecular biological marker of MDS; the degree of down-regulated c/ebpα has closely related to the progression of MDS.
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Proteína alfa Potenciadora de Unión a CCAAT/genética , Síndromes Mielodisplásicos/genética , Adolescente , Adulto , Anciano , Estudios de Casos y Controles , Femenino , Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , Síndromes Mielodisplásicos/patología , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Adulto JovenRESUMEN
OBJECTIVE: To investigate the frequency and clinical implication of JAK2 mutation in patients with myeloproliferative neoplasm(MPN)and the correlation between the mutation and thrombosis. METHODS: The clinical and laboratory data of 107 MPN patients was retrospectively analyzed. JAK2 mutation were detected with allele-specific polymerase chain reaction (AS-PCR) and sequencing. The significance of the mutation in disease diagnosis and molecular pathogenesis and the correlation between the mutation and thrombosis was analysed. RESULTS: JAK2 mutation was detected in 71 (66.4%) and thrombosis in 34 (31.8%) of the 107 MPN patients. Thrombosis occurred in 34.8% (16/46) of polycythemia vera (PV), 32.6% (14/43) of essential thrombocythemia (ET), and 22.2% (4/18) of primany myelofibrosis (PMF) patients. The difference among the 3 groups was not significant (χ(2) = 0.96, P > 0.05). The frequency of thrombosis in JAK2(+) MPN patients (82.4%, 28/34) was higher than that in JAK2(-) MPN patients (17.6%, 6/34) (χ(2) = 5.71, P < 0.05). The frequency of thrombosis in MPN patients > 60 years was higher (41.5%, 27/65) than that in patients < 60 years (16.7%, 7/42) (χ(2) = 7.28, P < 0.01). CONCLUSION: JAK2 V617F mutation occurs in significant percentage of Chinese patients with MPN. Patients with JAK2 mutation and older age are more succeptible to thrombosis. JAK2 mutation screening in patients with unknown thrombosis is helpful to reveal the underlying latent-MPN.
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Trastornos Mieloproliferativos , Neoplasias , Humanos , Mutación , Trastornos Mieloproliferativos/genética , Trombocitemia Esencial/genética , TrombosisRESUMEN
OBJECTIVE: To analyse the engraftment, transplant-related complications and survival after unrelated cord blood transplantation (UCBT) in patients with hematologic malignancies. METHODS: Twenty eight consecutive adult patients with hematological malignancies were treated with UCBT and 20 of them were advanced-stage diseases. Double or multiple UCB grafts were used for 18 patients, while single UCB graft for 10 patients. Myeloablative conditioning regimens were given to 26 cases and nonmyeloablative regimens to 2 cases. All patients were given a combination of cyclosporine (CsA) and mycophenolate mofetil (MMF) for graft-versus-host disease (GVHD) prophylaxis. RESULTS: Median time to neutrophil engraftment (≥ 0.5 × 10(9)/L) in 26 patients was 18 (14 - 37) days and platelet engraftment (≥ 20 × 10(9)/L) in 22 patients was 30 (25 - 49) days. Chimerism was weekly assessed by PCR analysis of short tandem repeat (STR) sequences in whole blood or bone marrow and 22 cases were confirmed of fully donor chimeric from 7 to 21 days after transplantation. Eighteen cases developed acute GVHD, greater than grade II in 1, and 6 of 22 patients who survived more than 100 days developed limited chronic GVHD. Eighteen cases were alive in hematologic remission at a median follow-up of 9.5 (2.5 - 72.0) months. The probability of event-free survival at 3 years was 56.7%. Two cases relapsed and 8 of 10 cases died of transplant related complications. CONCLUSIONS: UCBT could be safely and effectively used for adult patients with hematologic malignancies. Use of double UCB units is a strategy extending the feasibility of UCBT.
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Sangre Fetal , Neoplasias Hematológicas , Adulto , Enfermedad Injerto contra Huésped/prevención & control , Neoplasias Hematológicas/terapia , Trasplante de Células Madre Hematopoyéticas , Humanos , Acondicionamiento PretrasplanteRESUMEN
BACKGROUND: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective treatment for severe aplastic anemia (SAA). However, graft failure and graft-versus-host disease (GVHD) are major causes of the early morbidity in Allo-HSCT. METHODS: To reduce graft failure and GVHD, we treated fifteen patients with SAA using high- dose of HSCT with both G-CSF mobilized PB and BMSCs from HLA-identical siblings to treat patients with SAA. RESULTS: All patients had successful bone marrow engraftment. Only one patient had late rejection. Median time to ANC greater than 0.5 × 10(9)/L and platelet counts greater than 20 × 10(9)/L was 12 and 16.5 days, respectively. No acute GVHD was observed. The incidence of chronic GVHD was 6.67%. The total three-year probability of disease-free survival was 79.8%. CONCLUSION: HSCT with both G-CSF mobilized PB and BMSCs is a promising approach for heavily transfused and/or allo-immunized patients with SAA.
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Anemia Aplásica/terapia , Enfermedad Injerto contra Huésped/prevención & control , Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Antígenos HLA/inmunología , Movilización de Célula Madre Hematopoyética/métodos , Trasplante de Células Madre Hematopoyéticas/métodos , Adulto , Enfermedad Injerto contra Huésped/inmunología , Humanos , Hermanos , Donantes de TejidosRESUMEN
OBJECTIVE: To investigate the prevalence and the risk of natural anticoagulants such as plasma protein C (PC), protein S (PS) and antithrombin (AT) deficiency in thromboembolic patients with no evident acquired factors. METHODS: Clotting assays on French STAGO autoanalyzer were used to detect the activity of plasma PC, PS and AT in 85 patients with thrombotic disease and 50 sex and age matched healthy controls. RESULTS: Among the 85 enrolled patients (18 arterial and 67 venous thromboembolism), male to female ratio was 1.4 and the median age was 42 years (17-69). The activity of plasma PC, PS and AT in the pre-therapy thrombotic disease group, the thrombo-recurrence group, and the age < or = 45 years group were significantly lower than that is the healthy control group, the first thrombotic episodes group and the age > 45 years group respectively (P < 0.001, P < 0.01, P < 0.01). The overall deficiency rate of these three natural anticoagulants was 30.6%, PS deficiency was the commonest (10.6%), the second was PC deficiency (8.2%), AT deficiency and combined deficiency each accounted for 5.9%. CONCLUSION: The PC, PS and AT protein deficiencies are frequent in Chinese thromboembolic patients, they are the independent risk factors for the thrombotic events and recurrence.